Biomedical subjects

Amanda Blasius

Publications and source records attributed to Amanda Blasius.

3 recordsLinked to original sources

PubMed2006

Interferon-producing cells develop from murine CD31(high)/Ly6C(-) marrow progenitors.

In this study, we sorted total bone marrow (BM) into six distinct subsets based on surface expression of CD31 and Ly6C and investigated the capacity of these subsets to acquire characteristics of plasmacytoid dendritic cells (PDCs) after in vitro culture with FMS-like tyrosine kinase 3 ligand (Flt3-L). Cultured CD31(high)/Ly6C(-) cells were the only subset that consistently developed immunophenotypic, functional, and morphologic characteristics of PDCs. Culture of this subset resulted in expression of CD11c, B220, and the PDC-specific marker 440C and secretion of interferon-alpha (IFN-alpha) when stimulated with CPG ODN 2216. Cultured cells displayed the typical plasmacytoid morphology of PDCs with eccentrically located nucleus and mature lymphoid chromatin. Unlike conventional dendritic cells (CDCs) that can be generated from CD31(high)/Ly6C(-), CD31(+)/Ly6C(+), and CD31(-)/Ly6C(high) BM subpopulations, PDCs can only be derived from the CD31(high)/Ly6C(-) subset, the subset that reportedly contains the highest frequency of early and late cobblestone area forming cells (CAFC).

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PubMed2005

Plasmacytoid dendritic cells: in search of their niche in immune responses.

Plasmacytoid dendritic cells (pDCs) have been associated with several names and functions over time, reflecting the limited availability of specific markers and their ability to produce large amounts of type I interferons, present antigens, as well as prime disparate T-cell helper responses. Yet, there is increasing evidence that pDCs are a distinct cell type in the innate immune system. This review highlights aspects in which pDCs are unique in comparison to other antigen-presenting cells in regulating innate and adaptive immune responses.

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PubMed2003

A cell-surface molecule selectively expressed on murine natural interferon-producing cells that blocks secretion of interferon-alpha.

Natural interferon (IFN)-producing cells (IPCs) recognize certain viruses and DNA containing deoxycytidylate-phosphatedeoxyguanylate (CpG) motifs through the toll-like receptor (TLR) 9, resulting in secretion of IFN-alpha, interleukin 12 (IL-12), and proinflammatory chemokines. Human IPCs are found mainly in inflamed lymph nodes, where they are presumably recruited from the blood to activate both innate and adaptive responses to microbial infections. Demonstrating IPC recruitment and function in murine infection models has been difficult because multiple antibodies are required to distinguish IPCs from other immune cells and very few IPCs can be recovered from lymph nodes. Here we describe a monoclonal antibody (mAb) that exclusively detects murine IPCs in all lymphoid organs under both normal and inflammatory conditions. Using this antibody, we demonstrate that IPCs are normally present in the T-cell zone of lymph nodes and spleen and that inoculation of peripheral tissues with inflammatory stimuli triggers recruitment of IPC into sentinel lymph nodes, whether the stimuli are able to directly stimulate IPCs through TLR or not. Remarkably, we show that incubation of IPCs with the antibody in vitro or administration of the antibody in vivo dramatically reduce secretion of IFN-alpha in response to CpG DNA without causing IPC depletion. Thus, the antibody identifies an IPC-specific surface molecule that, when engaged, inhibits IFN-alpha secretion.

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